Condition category
Injury, Occupational Diseases, Poisoning
Date applied
19/04/2017
Date assigned
24/04/2017
Last edited
24/04/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Major trauma is damage caused to the body by an external source, such as a car accident or stabbing. It accounts for a significant number of deaths in the UK, and is one of the most frequent causes of death in people under the age of 45. One of the most common causes of death in trauma patients is uncontrolled bleeding. At present, standard treatment for severe bleeding involves giving patients blood transfusions. Until recently one out of every two people who received a massive blood transfusion (more than 10 pints) would die from their injuries. Two important studies involving bleeding trauma patients have been conducted in the last five years showing that early intervention is more effective after injury and may help save lives. Patients who have severe bleeding after injury develop a problem with their clotting system which means that they tend to bleed more. One of the main problems is due to low levels of fibrinogen, a clotting protein normally circulating in the bloodstream. Fibrinogen acts as the ‘glue’ which holds a blood clot together and at low levels, blood clots don’t form properly and bleeding can continue. Cryoprecipitate is a frozen blood component prepared from plasma (the liquid part of blood) and rich in fibrinogen. By giving patients cryoprecipitate early on to raise fibrinogen levels in bleeding trauma patients it may be possible to make blood clots more stable and reduce bleeding. The aim of this study is to find out whether or not giving cryoprecipitate treatment reduces death rates in trauma patients with severe bleeding.

Who can participate?
Trauma patients with severe bleeding who are taken to a Major Trauma Centre

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive standard care, which involves being treated with large blood transfusions through a drip. Those in the second group are treated with cryoprecipitate before they are given the blood transfusions. Participants in both groups are followed up for survival rates until study day 28 and then for up to one year using the Office for National Statistics. The Trauma Audit Research Network administers questionnaires to assess quality of life six months after injury.

What are the possible benefits and risks of participating?
There is a small chance that patients receiving cryoprecipitate early may raise their blood fibrinogen level higher than those receiving standard care and this may increase the risk of clots such as deep vein thrombosis (DVT), clots in the lungs, heart attacks and strokes. However, in small trauma studies to date there has been no evidence of an increased risk of developing clots. There are no anticipated additional risks associated with participating in this trial.

Where is the study run from?
23 NHS hospitals with Major Trauma Centres in England (UK)

When is the study starting and how long is it expected to run for?
February 2017 to February 2021

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Professor Karim Brohi
k.brohi@qmul.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Karim Brohi

ORCID ID

http://orcid.org/0000-0003-0643-8866

Contact details

Centre for Trauma Sciences
Blizard Institute
Queen Mary University of London
Whitechapel
London
E1 2AT
United Kingdom
+44 20 3594 0737
k.brohi@qmul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

34303

Study information

Scientific title

CRYOSTAT-2: A multi-centre, randomised, controlled trial evaluating the effects of early high-dose cryoprecipitate in adult patients with major trauma haemorrhage requiring major haemorrhage protocol (MHP) activation

Acronym

CRYOSTAT-2

Study hypothesis

The primary aim of this study is to test whether early high-dose fibrinogen supplementation with cryoprecipitate reduces all-cause mortality at 28 days in adult trauma patients with haemorrhagic shock and active bleeding.

Ethics approval

South Central REC C - Oxford, 12/04/2017, ref: 17/SC/0164

Study design

Randomised; Interventional; Design type: Treatment, Management of Care

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Injuries and emergencies, Primary sub-specialty: Injuries and emergencies; UKCRC code/ Disease: Injuries and Accidents/ Injuries involving multiple body regions

Intervention

Adult Trauma patients admitting to recruiting Major Trauma Centres, who are eligible for the trial, will be entered into the trial using an emergency waiver of consent. Patients on arrival will be incapacitated as a result of their injuries and ongoing bleeding and therefore will be unable to provide informed consent. Professional consultees (physicians who are not part of the study team) will provide approval for the patient to continue in the study until such time it is possible to speak with the patient and/or their next of kin.

Participants will be randomised to one of two groups using opaque sealed randomisation envelopes to enable rapid access and timely recruitment in the emergency setting.

Control group: Participants receive care using the tandard major haemorrhage protocol only. This involves administering red blood cells, fresh frozen plasma and platelets following a major haemorrhage protocol (MHP) as part of a balanced resuscitation.

Intervention group: Participants receive early cryoprecipitate – 3 pools (equivalent to 15 single units cryoprecipitate or 6g fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of admission in addition to the standard (local) major haemorrhage

Patients will be followed up for death up until study day 28 and for up to 1 year post admission with the Office for National Statistics. Follow up for quality of life will be undertaken at 6 months post injury via the Trauma Audit Research Network.

Intervention type

Drug

Phase

Phase III

Drug names

Cryoprecipitate

Primary outcome measures

All-cause mortality at 28 days as documented and confirmed in the patients medical notes by attending physicians. The primary cause of death will be documented and if possible categorised according to the following clinical causes:
1. Uncontrolled bleeding
2. Vascular occlusion (myocardial infarction, stroke)
3. Pulmonary embolism
4. Multi-organ failure
5. Traumatic brain injury
6. Multiple injury
7. Sepsis
8. Other (reason)

Secondary outcome measures

1. All-cause mortality (including death from bleeding) at 6 hours, 24 hours, 6 months and 12 months from admission as record in the patients medical notes during their admission and captured by the Office for National Statistics for up to 1 year post admission
2. Death from bleeding at 6 hours and 24 hours as recorded in the patients medical notes
3. Transfusion requirements, in numbers of units, for RBC, platelets, FFP & cryoprecipitate at 24 hours from admission, including pre-hospital transfusion as recorded in the patients medical notes
4. Destination of participant at time of discharge from hospital as recorded by the research team
5. Quality of life measures: EQ5D-5L and Glasgow Outcome Score at discharge and 6 months after injury captured by patient questionnaires administrated by the Trauma Audit Research Network
6. Hospital resource use up to discharge or day 28, including blood transfusions, surgical procedures, ventilator days, hours spent in critical care and in-patient stays measured by clinical data captured by the research teams in the Case Report Forms

Overall trial start date

07/02/2017

Overall trial end date

28/02/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. The participant is judged to be an adult (according to local practice, e.g. 16 years or older in UK) and has sustained severe traumatic injury
2. Deemed by the attending clinician to have on-going active haemorrhage
3. Requires activation of the local major haemorrhage protocol for management of severe blood loss
4. Has started or received at least one unit of any blood component

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1544; UK Sample Size: 1125

Participant exclusion criteria

1. The participant has been transferred from another hospital
2. The trauma team leader deems the patient inappropriate for the trial i.e. injuries deemed to be incompatible with life
3. More than 3 hours have elapsed from the time of injury

Recruitment start date

01/07/2017

Recruitment end date

30/06/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

John Radcliffe Hospital
Headley Way
Oxford
OX3 9UD
United Kingdom

Trial participating centre

Southampton Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

St George’s Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom

Trial participating centre

St Mary’s Hospital
Praed Street
London
W2 1NY
United Kingdom

Trial participating centre

Derriford Hospital
Derriford Road
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Southmead Hospital
Southmead Road
Bristol
BS10 5NB
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

Leeds General Infirmary
Great George St
Leeds
LS1 3EX
United Kingdom

Trial participating centre

Queen’s Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Queen Victoria Road
Newcastle-upon-Tyne
NE1 4LP
United Kingdom

Trial participating centre

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Royal Preston Hospital
Sharoe Green Lane
Preston
PR2 9HT
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Eastern Road
Brighton
BN2N 5BE
United Kingdom

Trial participating centre

University Hospital
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

University Hospital of North Staffordshire
Newcastle Road
Stoke on Trent
ST4 6QG
United Kingdom

Trial participating centre

Salford Royal Hospital
Scott Lane
Manchester
M6 8HD
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

University Hospital Aintree
Lower Lane
Liverpool
L9 7AL
United Kingdom

Sponsor information

Organisation

Queen Mary University of London

Sponsor details

JRMO
QMUL Innovation Department
5 Walden Street
London
E1 2EF
United Kingdom
+44 20 7882 7265
sponsorsresp@bartshealth.nhs.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal in 2022

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/06/2022

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes